Previously, we have shown that fluorescence spectroscopy can reliably differentiate atheroma from normal sites in necropsy specimens. To determine the feasibility of an in vivo catheter based fluorescence detection system which can be used for clinical laser angioplasty, 25 patients were studied either in the operating room or in the cardiac catheterization laboratory using a 325nm helium cadmium continuous laser excitation source and optical multichannel fluorescence analysis. Both excitation and fluorescence light was transmitted via a common flexible optical fiber bundle to and from remote coronary and aortic sites which were labelled either normal or abnormal based on direct observation or angioscopy. Analyzable spectra (n=124) were obtained from 92% of all sites and required flush fiber-tissue contact. Monomorphic fluorescence spectra from normal sites showed significant variations in peak position among patient subgroups. This inter and intrapatient variability of normal site peaks was for greater than previous necropsy data obtained in our laboratories. Advanced algorithms could distinguish normal sites from abnormal sites in most cases (p less than .005) but the sensitivity of in vivo abnormal site recognition (67%) was less than in vitro data. We conclude from this preliminary study that fluorescence via optical fibers can be recorded safely and reliably in patients. In vivo tissue optics and other factors may result in higher inter and intrapatient variability of normal site peaks. Fluorescence detection of atheroma in patients, although possible, is somewhat less sensitive when compared to in vitro specimens. However, we believe that the technique of common fiber fluorescence spectroscopy as a means of target recognition can be incorporated within a dual laser computer based system for tissue ablation.